Advanced Paternal Age Does Not Affect Medically-Relevant Obstetrical and Perinatal Outcomes following IVF or ICSI in Humans with Donated Oocytes

Abstract

Background: Concomitant with delays in childbearing, concerns have been raised of whether advanced paternal age is associated with adverse reproductive outcomes, but the evidence is controversial in part due to the uncertain threshold in which to consider advanced paternal age and confounding maternal factors. This retrospective study aimed to evaluate the effect of paternal age on reproductive outcomes related to the pregnancy and perinatal health of the offspring.

Methods: We retrospectively evaluated 16,268 cases of patients who underwent IVF or ICSI (using autologous sperm and donated oocytes, between January 2008 and March 2020, at Spanish IVIRMA clinics. Patients were divided based on paternal age at conception [≤30 (n = 204), 31-40 (n = 5752), and >40 years (n = 10,312)], and the differences in obstetrical and perinatal outcomes were analyzed by descriptive analysis, followed by univariate and multivariate analysis.

Results: Fathers 31-40 and >40 years old were associated with lower odds of caesarean delivery [AOR 0.63 (95% CI, 0.44-0.90; p = 0.012) and AOR 0.61 (95% CI, 0.41-0.91; p = 0.017), respectively] and longer pregnancies [ARC 5.09 (95% CI, 2.39-7.79; p < 0.001) and ARC 4.54 (95% CI, 1.51-7.58; p = 0.003), respectively] with respect to fathers ≤30 years old. Furthermore, fathers aged 31-40 years old had lower odds of having a female infant (AOR, 0.70; 95% CI, 0.49-0.99; p = 0.045) than those ≤30. The rest of obstetrical and perinatal outcomes, which we deemed more medically-relevant as they were considered serious for health, were comparable between groups with our adjusted model.

Conclusions: Despite this hopeful message to fathers of advanced paternal age, future studies should consider the short- and long-term outcomes of the offspring and try to better elucidate the associations of advanced paternal age with reproductive outcomes and the molecular mechanisms underlying the observed associations.

Keywords: assisted reproductive technology (ART); donated oocytes; obstetrical outcomes; offspring’s health; paternal age; perinatal outcomes; pregnancy.